Altered Motor Function and Graft Survival Produced by Basic Fibroblast Growth Factor in Rats with 6-OHDA Lesions and Fetal Ventral Mesencephalic Grafts Are Associated with Glial Proliferation

Abstract

Basic fibroblast growth factor (bFGF) promotes the survival and growth of dopaminergic neurons. We have investigated the effect of treating fetal ventral mesencephalon with bFGF or nerve growth factor (NGF) on the subsequent survival and function of grafted dopaminergic neurons implanted into the striatum of rats with a unilateral 6-hydroxydopamine lesion. Animals implanted with fetal ventral mesencephalon mixed with bFGF, but not with NGF, displayed a more rapid compensation in motor behavior up to 9 weeks after graft implantation. bFGF, but not NGF, produced an increase in the number of tyrosine hydroxylase (TH)-positive neurons, a larger graft volume, and longer neurite outgrowth in comparison to control grafts. bFGF also increased the number of glial fibrillary acidic protein (GFAP)-positive astrocytes within the grafts. The increased number of GFAP-positive astrocytes induced by bFGF correlated with the increase in the number of TH-positive neurons, with graft volume and with neurite outgrowth. These findings support the use of bFGF to promote the functional integration of fetal ventral mesencephalon grafts into the denervated host brain and suggest that its action may be indirectly mediated through glial cells.